(a) Technical Field
The present disclosure relates to a novel compound that functions as a calcium-dependent chloride channel blocking agent.
(b) Background Art
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.
A chloride channel derived from different kinds of cells has a characteristic of being activated by a calcium ion concentration ranging from 0.2 to 5 mM in cytoplasm. The existence of the chloride channel was firstly found in a frog egg cell in the 1980s. It was found in the frog egg cell that, when a calcium-sensitive chloride channel is open due to an increase in calcium ion concentration during fertilization, depolarization of a membrane occurs, which in turn, prevents sperm cells from flowing into the membrane. Thereafter, the existence of a calcium-dependent chloride channel in a variety of neural cells and other cells has been demonstrated.
A chloride channel has different functions depending upon cells from which the chloride channel is derived. Major functions of the chloride channel known in the related art may include epithelial secretion, membrane excitability of cardiac muscle and neuronal cells, conduction of olfactory impulses, pulse control, control of a photoreceptor reaction, or the like. Accordingly, a compound having chloride channel blocking activity may be used as an effective drug for treating, preventing and/or alleviating diseases including: (i) bone diseases related to osteoclasts such as osteoporosis, postmenopausal osteoporosis, Type III osteoporosis, osteolytic bone metastasis associated breast cancer, invasion of osteolytic cancer, Paget's disease of bone, or the like; (ii) tumor cell proliferative diseases such as cancer, prostate cancer, lung cancer, breast cancer, bladder cancer, kidney cancer, colon cancer, stomach cancer, pancreas cancer, ovarian cancer, melanoma, liver cancer, sarcoma, lymphoma, or the like; (iii) diseases related to ocular vascular formation such as wet macular degeneration, age-related macular degeneration (AMD), retinopathy, diabetic retinopathy, proliferative diabetic retinopathy, diabetic macular edema (DME), ischemic retinopathy (i.e., retinal vein occlusion or retinal artery occlusion), retinopathy of prematurity, neovascular glaucoma, corneal neovascularization, or the like; (iv) diseases caused by reduction of intraocular pressure such as ocular hypertension, open angle glaucoma, chronic open angle glaucoma, closed angle glaucoma, ciliary hyperemia caused by closed angle glaucoma, or the like; (v) rheumatoid arthritis; (vi) psoriasis; (vii) sickle-cell anemia, and the like (see International Patent Laid-Open Publication No. 2004/111017).
As such, studies into the various and important functions of the calcium-dependent chloride channel have continued about 20 years since 1980s. However, research into mechanisms relating to physiological functions and control thereof has still been insufficient. Such related conditions continue as an appropriate chloride channel blocking agent has not yet been developed, therefore, the development of a chloride channel blocking agent which exhibits adequate reliability and selectivity is urgently needed.
Under the foregoing circumstances, the present inventors have developed an anthranilic acid compound represented by formula A below, as a calcium-dependent chloride channel blocking agent, which was granted as a patent in Korea with Korean Patent No. 892,591:

wherein, R1 and R2 are independently each selected from a group consisting of a hydrogen atom; halogen atom; linear, branched or cyclic alkyl having 5 to 16 carbon atoms; linear or branched substituted alkyl having 1 to 16 carbon atoms; substituted or non-substituted aryl having 6 to 12 carbon atoms; alkoxy having 1 to 8 carbon atoms; substituted alkoxy having 1 to 8 carbon atoms; and a nitro group, provided that R1 and R2 cannot be simultaneously hydrogen atoms; and; R3 is a hydrogen atom or nitro group.
The anthranilic acid compound described in the present invention is a novel compound not disclosed in the foregoing registered patent and has a characteristic in a chemical structure thereof wherein a naphthylamino group having various substituents is substituted at a C2 position of a mother nucleus of anthranilic acid. Alternatively, as compared to the anthranilic acid compound represented by Formula A which is substituted by a phenyl group at a C2 position, the anthranilic acid compound of the present invention having a naphthylamino group substituted at a C2 position has more superior efficacy as a calcium-dependent chloride channel blocking agent.